Sunday, October 23, 2005

Statins and clopidogrel together: Do we have the final answer?

Not yet, in spite of the profusion of studies that have been published ever since the first report in Circulation of an in vitro interaction between clopidogrel and atorvastatin. Clopidogrel is a pro-drug which is metabolized to the active drug by CYP3A4, while atorvastatin is metabolized by the same enzyme. Atorvastatin attenuated the anti-platelet action of clopidogrel in vitro, in a dose dependent fashion.

The latest offering is a recent study in the European Journal of Clinical Investigation in which the effect of clopidogrel on platelet function was tested during concomitant administration of several statins in healthy subjects. Simvastatin and fluvastatin, but not atorvastatin, pravastatin or rosuvastatin, attenuated the effect of clopidogrel. The dose of atorvastatin was only 20mg daily.

An earlier study had concluded that none of five statins, including atorvastatin, attenuated the anti-platelet effect of clopidogrel. The range of atorvastatin doses in that study was 10-40mg.

Despite several studies and substantial expert opinion pointing to the safety of concomitant use of statins and clopidogrel I remain concerned because of a lack of data concerning statin dosage effects. My specific concern is that the in vitro evidence suggests that the interaction is dose dependent, and the highest atorvastatin dose purportedly shown to be safe with clopidogrel was 40mg. This is particularly important in view of recent recommendations that 80mg atorvastatin be initiated in the early period following acute coronary syndrome.